年龄相关的肝损伤和纤维化与免疫细胞群体的关联。
Association of age-dependent liver injury and fibrosis with immune cell populations.
机构信息
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
出版信息
Liver Int. 2013 Sep;33(8):1175-86. doi: 10.1111/liv.12202. Epub 2013 May 26.
BACKGROUND & AIMS: The liver's response to injury is fibrosis, and when chronic, cirrhosis. Age is a critical factor impacting many immune-mediated processes, potentially including the liver's wounding response to injury.
METHODS
The effects of age on acute and chronic liver injury were evaluated using a carbon tetrachloride model in mice. Lymphocyte and macrophage populations were assessed by flow cytometry and immunohistochemical analysis.
RESULTS
Acute liver injury was greater in 18-month-old (old) mice than in 9-month-old (middle-aged) mice as judged by changes in aminotransferases. Similarly, livers of 18-month-old mice had a significantly greater fibrogenic response to injury than did livers of 9-month-old mice after chronic injury (assessed by col1α1 mRNA expression, morphometric analysis and hydroxyproline measurement). Interestingly, livers from young mice (6 weeks old) also exhibited an increase in fibrogenesis compared to 9-month-old mice, albeit not to the same degree as in old mice. Consistent with a role for macrophages in fibrogenesis, the number of liver macrophages in young and 9-month-old mice increased, while in chronically injured livers of 18-month-old mice, the number of macrophages was reduced, and was less than in the livers of young and 9-month-old injured livers.
CONCLUSIONS
Our data indicate that the fibrogenic response to injury varies substantially with age, and moreover that macrophage recruitment and dynamics may be an important component in differential age-associated fibrotic disease.
背景与目的
肝脏对损伤的反应是纤维化，当慢性时则是肝硬化。年龄是影响许多免疫介导过程的关键因素，可能包括肝脏对损伤的创伤反应。
方法
使用四氯化碳模型在小鼠中评估年龄对急性和慢性肝损伤的影响。通过流式细胞术和免疫组织化学分析评估淋巴细胞和巨噬细胞群体。
结果
与 9 个月大（中年）的小鼠相比，18 个月大（老年）的小鼠的急性肝损伤更严重，这可以通过氨基转移酶的变化来判断。同样，与 9 个月大的小鼠相比，慢性损伤后 18 个月大的小鼠的肝脏具有更大的纤维生成反应（通过 col1α1 mRNA 表达、形态计量分析和羟脯氨酸测量评估）。有趣的是，与 9 个月大的小鼠相比，年轻（6 周龄）小鼠的肝脏也表现出纤维生成增加，尽管程度不及老年小鼠。与巨噬细胞在纤维化中的作用一致，年轻和 9 个月大的小鼠的肝脏巨噬细胞数量增加，而在 18 个月大的慢性损伤肝脏中，巨噬细胞数量减少，且少于年轻和 9 个月大的受损肝脏。
结论
我们的数据表明，对损伤的纤维生成反应随年龄有很大差异，而且巨噬细胞募集和动态可能是年龄相关纤维性疾病差异的一个重要组成部分。
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